• Toxicological Research
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• v.17
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• pp.117-125
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• 2001

Envenoming by Russells viper causes a broad spectrum of renal impairment. Renal failure is an important complication in patients bitten by Russells viper. Experimental work in animals and in vitro has elucidated pathophysiological mechanisms that contribute to life threatening complications and have suggested possibilities for therapeutic intervention. The evidence in experimental animals regarding mechanisms of venom action in relation to changes in either extrarenal or intrarenal factors is presented. The cardiovascular system and renal hemodynamics are affected by venom. Reductions of renal function including renal hemodynamics are associated directly with changes in general circulation during envenomation. Possible endogenous mechanisms for releasing the hormone inducing renal vasoconstriction after envenomation are evident. Hormonal factor such as the catecholamine, prostaglandin and renin angiotensin systems induce these changes. Direct nephrotoxicity of venom action is studied in the isolated per-fused kidney. Characteristic polarization of the cell membrane, changes of mitochondrial activity and Na-K ATPase in renal tubular cells are observed. Changes in renal function and the cardiovascular system are observed of ter envenomation and are reversed by the administration of Russells viper antivenom (purified equine immunoglobulin, $Fab_2$ fragment). The neutralizing effects are more efficient when the intravenous injection of antivenom is given within 30 min after the envenomation.

• Journal of Pharmacopuncture
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• v.25 no.2
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• pp.114-120
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• 2022

Objectives: Antivenom serums have been used extensively for over a century and are the only effective treatment option for snake bites and other dangerous animal envenomations. In therapeutic serum centers, a wide range of antivenoms is made from animal serum, mainly equine and sheep, that are immunized with single or multiple venoms. This work aimed to use caprylic acid (CA) to purify therapeutic snake antivenom. Methods: Plasma was obtained from equine immunized with a mixture of venoms. Immunized plasma was obtained by precipitation of different concentrations (2-5%) of CA. This methodology was compared to that based on ammonium sulfate (AS) precipitation. Sediment plasma proteins were purified by ion-exchange chromatography. Protein assay, SDSPAGE, and agar gel diffusion were performed. Results: The total protein precipitation with AS was higher than precipitation with CA, but the best results were obtained when CA was added to the plasma until a final CA concentration of 5% was reached. Chromatography and electrophoresis indicated a stronger band for the 5% CA, and the gel diffusion assay showed antigen-antibody interaction in the purified serum. Conclusion: The use of CA compared to the routine method for purifying hyperimmune serums is a practical and cost-effective method for preparing and producing therapeutic serums. It constitutes a potentially valuable technology for alleviating the critical shortage of antivenom in Iran.

• Journal of The Korean Society of Clinical Toxicology
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• v.20 no.1
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• pp.22-24
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• 2022

Elapid snakes have neurotoxic venom which causes diverse neuroparalytic manifestations, including fatal respiratory failure. In South Korea, since elapid snakebites are very rare, the cobra antivenom, which is effective against neurotoxicity, was only introduced recently. Most physicians in South Korea have little experience in the treatment of patients who have been bitten by elapid snakes. A 19-year-old man was brought to the emergency department with sudden diplopia, 1 hour after a snakebite on the left 2nd finger. The patient presented with drowsiness and complained of mild dizziness and binocular diplopia. After 1 hour, he had sudden onset of dyspnea and dysphagia and appeared to be agitated. He was immediately intubated and received mechanical ventilation as he was unable to breathe on his own. A total of 2.5 mg of neostigmine diluted with normal saline was slowly infused, and 1 vial of cobra antivenom was infused for an hour, 5 times every 2 hours, for a total of 5 vials. He slowly recovered self-breathing; on the 3rd day of hospitalization, he showed tolerable breathing and was extubated. He was discharged without any neurological deficits or other complications.

• CELLMED
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• v.10 no.4
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• pp.30.1-30.4
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• 2020

Background: Tiryaq-e-arba is a polyherbal Unani antidote/antivenom formulation used in the management of poisoning due to snake bite, scorpion bite as well as in cold poisons since time immemorial. Objectives: Tiryaq-e-arba was not evaluated scientifically before this study carried out, therefore it was studied for antivenom activity by testing on plasma fibrinogen level in Russell's Viper envenomation in rabbits. Material &Methods: The anti-venom activity of the test drug was studied by observing its effect on plasma fibrinogen level in Russell's Viper envenomation in rabbits by the method of Netelson. Results: The plasma fibrinogen level was found to be 171±665.04 mg/100 ml of blood, 36.18±1.12 mg/100 ml of blood, 33.14±0.52 mg/100 ml of blood and 17.9±1.65 mg/100 ml of blood at 0, 1, 3 and 6 hours respectively in control animals while in the test animal it was found to be 157.13±3.44 mg/100 ml of blood, 41.13±2.69 mg/100 ml of blood, 62.09±1.65 mg/100 ml of blood and 54.39±0.73 mg/100 ml of blood respectively. The test showed that though the plasma fibrinogen level in the test lower at 0 hour but it was greater in the control animals at 1, 3 and 6 hours. The increase in plasma fibrinogen level in the test animals at 3 and 6 hours was statistically significant (P<0.001). Conclusions: The finding of the present study was that Tiryaq-e-arba possesses antivenom activity which scientifically support the Unani claim that it is Dafe-Sumoom-al-Hevan (Antivenom or Antidote) and the use of this preparation in corresponding diseases.

• Journal of Pharmacopuncture
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• v.23 no.4
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• pp.212-219
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• 2020

Objectives: Nowadays cancer treatment is an important challenge in the medical world that needs better therapies. Many active secretions produced by insects such as honey bees used to discover new anticancer drugs. Bee venom (BV) has a potent anti inflammatory, anti cancer and tumor effects. The aim of present study is evaluation of anticancer effects induced by Apis mellifera venom (AmV) on cell Lines. Methods: AmV was selected for study on cancer cell lines. Total protein, molecular weight and LD50 of crude venom were determined. Then, cells were grown in Dulbecco's Modified Eagle medium supplemented with 10% fetal bovine serum and 1% antibiotics. The A549, HeLa and MDA-MB-231 cell Lines were exposed by different concentration of AmV. The morphology of cells was determined and cell viability was studed by MTT assay. Evaluation of cell death was determined by and DNA fragmentation. Results: The results from MTT assay showed that 3.125 ㎍/mL of A549, 12.5 for HeLa and 6.25 ㎍/mL of MDA-MB-231 killed 50% of cells (p < 0.05). Morphological analysis and the results from hoescht staining and DNA fragmentation indicated that cell death induced by AmV was significantly apoptosis. Conclusion: The data showed that using lower dosage of AmV during treatment period cause inhibition of proliferation in time and dose dependant manner. Findings indicated that some ingredients of AmV have anticancer effects and with further investigation it can be used in production of anticancer drugs.

• Journal of The Korean Society of Clinical Toxicology
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• v.20 no.2
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• pp.45-50
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• 2022

Purpose: This study utilizes the NEDIS (National Emergency Department Information System) database to suggest a predictive model for snakebite and envenomation in Korea by analyzing the geographical distribution and seasonal variation of snakebite patients visiting the ER. Methods: This was a retrospective study on snakebite patients visiting the ER using the NEDIS database from January 2014 to December 2019. The subjects include patients with the KCD (Korea Standard Classification of Disease) disease code T63.0 (Toxic effect of contact with snake venom). Geographical location, patient gender, patient age, date of ER visit, treatment during the ER stay, and disposition were recorded to analyze the geographical distribution and seasonal variation of snakebite patients in Korea. Results: A total of 12,521 patients were evaluated in this study (7,170 males, 54.9%; 5,351 females, 40.9%). The average age was 58.5±17.5 years. In all, 7,644 patients were admitted with an average admission time of 5.04±4.7 days, and 2 patients expired while admitted. The geographical distribution was Gyeongsang 3,370 (26.9%), Cheonra 2,692 (21.5%), Chungcheong 2,667 (21.3%), Seoul Capital area 1,999 (16.0%), Kangwon 1,457 (11.6%), and Jeju 336 (2.7%). The seasonal variation showed insignificant incidences in winter and higher severity in spring and summer than in fall: winter 27 (0.2%), spring 2,268 (18.1%), summer 6,847 (54.7%), and fall 3,380 (27.0%). Conclusion: Patients presenting with snakebites and envenomation in the emergency room were most common in the Gyeongsang area and during summer. The simple seasonal model predicted that 436 snakebites and 438 envenomation cases occurred in July and August. The results of this study can be applied to suitably distribute and stock antivenom. Appropriate policies can be formed to care for snakebite patients in Korea.

• Toxicological Research
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• v.34 no.3
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• pp.191-197
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• 2018

In 2015, a candidate for the second national reference standard (NRS) of Gloydius snake venom was produced to replace the first NRS of Gloydius snake venom. In the present study, the potencies of the candidate were determined by a collaborative study, and the qualification of the candidate was estimated. The potencies of the candidate were determined by measuring the murine lethal titers and lapine hemorrhagic titers of venom against the regional working reference standard (RWRS) for antivenom using the methods described in the previous report for the first NRS of Gloydius snake venom. Three Korean facilities contributed data from a total of 30 independent assays. Subsequently, two foreign national control research laboratories contributed to this collaborative study. The results were calculated using the Reed-Muench method for lethality and determined using a mixed-effects model for hemorrhage. The general common potencies of the lethal and hemorrhagic titers were obtained from the results of the 30 tests performed at three Korean facilities. The results are expressed in micrograms for 1 test dose (TD) with a 95% confidence interval as follows: a lethal titer of $90.13{\mu}g/TD$ (95% confidence interval = $87.39{\sim}92.86{\mu}g$) and a hemorrhagic titer of $10.80{\mu}g/TD$ (95% confidence interval = $10.46{\sim}11.14{\mu}g$). In addition, the candidate preparation showed good quality evaluation according to the results of the quality estimation of the candidate and is judged to be suitable to serve as the Korean NRS for snake venom. In conclusion, the second NRS of Gloydius snake venom was established in this study and will be used for national quality control, including a national lot release test of Korean antivenom products.

• Journal of Pharmacopuncture
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• v.18 no.4
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• pp.7-11
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• 2015

Objectives: Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations $(SDs)={\pm}0.71$; however, clotting was observed in the control group 13.8 s, $SDs={\pm}0.52$. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The $LD_{50}$ of the crude BV was found to be $177.8{\mu}g/mouse$. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase $A_2(PLA_2)$ and melittin, and that can increase the blood clotting times in vitro.

• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.225-230
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• 2016

Objectives: Mellitine, a major component of bee venom (BV, Apis mellifera), is more active against gram positive than gram negative bacteria. Moreover, BV has been reported to have multiple effects, including antibacterial, antivirus, and anti-inflammation effects, in various types of cells. In addition, wasp venom has been reported to have antibacterial properties. The aim of this study was to evaluate the antibacterial activity of BV against selected gram positive and gram negative bacterial strains of medical importance. Methods: This investigation was set up to evaluate the antibacterial activity of BV against six grams positive and gram negative bacteria, including Staphylococcus aureus (S. aureus), Salmonella typhimurium, Escherichia coli (E. coli) O157:H7, Pseudomonas aeruginosa, Burkholderia mallei and Burkholderia pseudomallei. Three concentrations of crude BV and standard antibiotic (gentamicin) disks as positive controls were tested by using the disc diffusion method. Results: BV was found to have a significant antibacterial effect against E. coli, S. aureus, and Salmonella typhyimurium in all three concentrations tested. However, BV had no noticeable effect on other tested bacteria for any of the three doses tested. Conclusion: The results of the current study indicate that BV inhibits the growth and survival of bacterial strains and that BV can be used as a complementary antimicrobial agent against pathogenic bacteria. BV lacked the effective proteins necessary for it to exhibit antibacterial activity for some specific strains while being very effective against other specific strains. Thus, one may conclude, that Apis mellifera venom may have a specific mechanism that allows it to have an antibacterial effect on certain susceptible bacteria, but that mechanism is not well understood.

• Journal of Pharmacopuncture
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• v.22 no.3
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• pp.140-146
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• 2019

Objectives: Venomous fishes have different pharmacological effects and are useful. Among the venomous fish, stonefishes; especially Pseudosynanceia melanostigma has various pharmacological effects on the nervous, muscular and cardiovascular system of humans. In this study, toxicological characteristics, some blood effects, pharmacological and enzymatic properties of Pseudosynanceia melanostigma venom was investigated. Methods: Crude venom purified by using gel filtration chromatography and the molecular weights of the venom and its fractions were estimated. The approximate LD values of this venom were determinedand the effects of LD50 dose on the blood of rabbits were studied. Hemolytic and Hemorrhagic activity of the venom sample was determined. In this case coagulation tests were performed. Results: The LD50 of the Pseudosynanceia melanostigma crude venom was also determined to be $194.54{\mu}g/mouse$. The effect of two doses of LD50 showed a non-significant differences decrease in RBCs and MCV. In other cases, the results showed significant differences in WBC, Plt, Hb, MCH, MCHC and HCT; also it's showed a significant decrease. WBC count showed a significant increase with two doses of LD50 groups. The prothrombin time and partial prothrombin time were increased after venom treatment. As well as bleeding and clotting time were increased. According to the results, a minimum dose for Haemorrhagic effect $40{\mu}g$ was obtained. Conclusion: Venom of Pseudosynanceia melanostigma has inhibitory effect on platelet aggregation that can be used to design and develop of anticoagulant drugs.